Abstract

Background: Gastric cancer (GC) remains one of the most malignant tumors around the world, and an accurate model that reliably predicts survival and therapeutic efficacy is urgently needed. As a novel predictor for prognosis in a variety of cancers, immune-related long noncoding RNA pairs (IRlncRNAPs) have been reported to predict tumor prognosis. Herein, we integrated an IRlncRNAPs model to predict the clinical outcome, immune features, and chemotherapeutic efficacy of GC.Methods: Based on the GC data obtained from The Cancer Genome Atlas (TCGA) database and the Immunology Database and Analysis Portal (ImmPort), differentially expressed immune-related long noncoding RNAs (DEIRlncRNAs) were identified. Least absolute shrinkage and selection operator (LASSO) regression and Cox regression analysis were used to select the most appropriate overall survival (OS)-related IRlncRNAPs to develop a prognostic signature. The riskScore of each sample was calculated by comparing the long noncoding RNA expression level in each IRlncRNAP. Based on the riskScore for each patient, GC patients were divided into high- and low-risk groups. Then, the correlation of the signature and riskScore with OS, clinical features, immune cell infiltration, immune-related gene (IRG) expression and chemotherapeutic efficacy in GC was analyzed.Results: A total of 107 DEIRlncRNAs were identified which formed 4297 IRlncRNAPs. Fifteen OS-related IRlncRNAPs were selected to develop a prognostic model. GC patients could be accurately classified into high- and low-risk groups according to the riskScore of the prognostic model. The 1-, 2-, 3-, and 5-year receiver operating characteristic (ROC) curves for the riskScore were drawn and the area under the curve (AUC) values were found to be 0.788, 0.810, 0.825, and 0.868, respectively, demonstrating a high sensitivity and accuracy of this prognostic signature. Moreover, the immune-related riskScore was an independent risk factor. Patients showed a poorer outcome within the high-risk group. In addition, the riskScore was found to be significantly correlated with the clinical features, immune infiltration status, IRG expression, and chemotherapeutic efficacy in GC.Conclusion: The prognostic model of IRlncRNAPs offers great promise in predicting the prognosis, immune infiltration status, and chemotherapeutic efficacy in GC, which might be helpful for the selection of chemo- and immuno-therapy of GC.

Highlights

  • Gastric cancer remains one of the most malignant tumors around the world

  • 107 IRlncRNAs were differentially expressed in Gastric cancer (GC) and paracancerous tissues (FDR 2) (Figure 1A), of which 96 were up-regulated and 11 were down regulated (Figure 1B and Supplementary Table 1)

  • We evaluated the prognostic value of clinicopathological characteristics and IRlncRNAPs riskScore by univariate Cox regression analysis, the results illustrated a strong association between the riskScore and the overall survival (OS) of GC patients (HR = 1.353, 95%CI 1.274– 1.437, and P < 0.001) (Figure 4C)

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Summary

Introduction

Gastric cancer remains one of the most malignant tumors around the world. The 5-year survival rate among advanced GC remains low, reported to be under 20% (Thomassen et al, 2014). Only a small portion of patients achieve survival benefits from immunotherapy. A model to accurately predict the efficacy of immunotherapy and prognosis in GC patients is urgently needed. Gastric cancer (GC) remains one of the most malignant tumors around the world, and an accurate model that reliably predicts survival and therapeutic efficacy is urgently needed. As a novel predictor for prognosis in a variety of cancers, immunerelated long noncoding RNA pairs (IRlncRNAPs) have been reported to predict tumor prognosis. We integrated an IRlncRNAPs model to predict the clinical outcome, immune features, and chemotherapeutic efficacy of GC

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